The replacement of damaged or diseased tissues or organs by transplantation has been and continues to be a long-standing goal of medicine towards which tremendous progress has been made. Controlling rejection while avoiding the adverse side effects of immunosuppressive agents is pivotal to successful transplantation. Rejection is characterized by perivascular infiltration of killer T-lymphocytes, which cause cellular necrosis if not checked. Since early rejection can be silent, it is important to detect it before necrosis occurs. Immunologic monitoring of activated T-lymphocytes in peripheral blood offers clues to the timing of a rejection process but has not been sufficiently reliable to dictate anti-rejection therapy.
Immunosuppressive therapy regimens vary but usually include therapy with cyclosporine, azathioprine, and prednisone. However, there are adverse side effects of these agents. Thus, careful monitoring of the side effects is extremely important. Such side effects include nephrotoxicity, bone marrow suppression, and opportunistic infections.
The most serious problem restricting the use of allografts is an immunological one. Because their cellular constituents express on their surfaces a variable number of genetically determined transplantation antigens, which are lacking in the host, allografts provoke a defensive type of reaction analogous to that incited by pathogenic microorganisms. As a consequence, after a transient initial period of apparent well being, there is often a functional deterioration in the graft associated with its progressive destruction. The host response, known as the allograft rejection, is expressed by the generation of a variety of putative immunological effectors, including cytotoxic antibodies and effector lymphocytes of various types. The destructive process varies somewhat according to the type of allograft involved as well as the degree of antigenic disparity between donor and recipient; for example, hyperacute rejection of kidneys is mediated by antibodies whereas acute rejection is a lymphocyte-mediated process.
Therefore, mammalian systems recognize foreign materials such as bacteria, viruses, penetrating or surgically implanted objects, or xenograft tissue. Upon binding to sites on these foreign entities, the cascade of events occurs that notify immune cells to surround such material and release cytotoxic materials as well as stimulate fibrin deposition to isolate the material.
Nearly all binding of cell surfaces occurs not through covalent or ionic bond formation, but through dipole moment attraction and hydrogen bond formation. As opposed to ionic or covalent bond formation, dipole moment and hydrogen bond formation require comparatively little energy. Upon close proximity to oppositely charged moieties, or electron donor and electron accepting atoms, such attractive forces are sufficient to allow proteins on cell surfaces to interact. By preventing such interactions from occurring, immune cells such as lymphocytes, macrophages, or neutrophils cannot bind to foreign materials. Without such binding, the materials are not recognized as foreign. Connective tissue protein such as fibrin forms initial attachment by binding positively charged (electron accepting) atoms to negatively charged (electron donating) oxygen atoms of the carbonyl groups. This provides the means of isolating foreign substances by dipole moment or hydrogen bonding interaction.
All proteins have electron accepting amine groups and electron donating carbonyl groups as part of each amino acid. Thus, polymer coatings that have electron accepting groups (amine, hydrogen, or other cationic species) will form attachments to both the cell surface and connective tissue protein carbonyl groups. Polymer coatings such as acrylates, polyesters, polyethylene glycol, polyvinilidine fluoride that contain exposed groups with a negative moment such as halogens or oxygen, attract the positive amine groups of proteins in cell surfaces. Likewise, polymer coatings that contain positively charged groups such as polyamides, attract the negative polar moment of halogens, oxygens, sulfone, sulfate and other groups.
Accordingly, there is needed a polymer coating which will not evoke the immune response for transplantation and other uses.